Substrate effects on the dynamics of neurite growth in vitro: a quantitative multi-parametric analysis

Embryonic chick dorsal root ganglia were cultured in serum-free medium on natural (collagen, fibronectin and hyaluronic acid) and artificial (polylysine and polyornithine) substrata. The movement of individual growth cones was quantified by measuring five parameters using time-lapse cinematography combined with a digitizing-computer system, and the neurite behaviour was compared between the different substrata with multivariate statistical methods. For each substratum, the morphometry of the growth cone was quantified by measuring six morphological parameters. The most discriminative parameters proved to be mean velocity and straightness index for neurite extension, and projected area and cumulated length of filopodia for growth cone morphometry. A good correlation was obtained between behavioural and morphological parameters and the larger the cone area and the filopodia length, the faster and the straighter the neuritic growth. Both quantitative analyses showed highest values for polyornithine and the lowest for hyaluronic acid, and divided the substrata into two opposite groups, artificial and natural. It is concluded that growth cone behaviour and conformation is modulated by substratum properties.     

Impact of the age of transfused red blood cells in the trauma population: A feasibility study

Following injury, transfusion of red blood cells (RBCs) of increased storage duration has been associated with an increased morbidity and mortality. Prospective trials focusing on the impact of the storage age of RBCs in severely bleeding trauma patients have failed to accrue patients. This has been attributed to an inability to maintain a large inventory of fresh RBCs, and the difficulties in obtaining consent in severely bleeding trauma patients. To address these issues, we performed a prospective, observational pilot study to evaluate the feasibility of conducting a trial focusing on RBC age in patients following injury.     

Long-term male-specific chronic pain via telomere- and p53‑mediated spinal cord cellular senescence

Mice with experimental nerve damage can display long‑lasting neuropathic pain behavior. We show here that 4 months and later after nerve injury, male but not female mice displayed telomere length (TL) reduction and p53‑mediated cellular senescence in the spinal cord, resulting in maintenance of pain and associated with decreased lifespan. Nerve injury increased the number of p53‑positive spinal cord neurons, astrocytes, and microglia, but only in microglia was the increase male‑specific, matching a robust sex specificity of TL reduction in this cell type, which has been previously implicated in male‑specific pain processing. Pain hypersensitivity was reversed by repeated intrathecal administration of a p53‑specific senolytic peptide, only in male mice and only many months after injury. Analysis of UK Biobank data revealed sex-specific relevance of this pathway in humans, featuring male‑specific genetic association of the human p53 locus (TP53) with chronic pain and a male-specific effect of chronic pain on mortality. Our findings demonstrate the existence of a biological mechanism maintaining pain behavior, at least in males, occurring much later than the time span of virtually all extant preclinical studies.     

Attenuation Coefficient Estimation of Normal Placentas

Attenuation coefficient estimation has the potential to be a useful tool for placental tissue characterization. A current challenge is the presence of inhomogeneities in biological tissue that result in a large variance in the attenuation coefficient estimate (ACE), restricting its clinical utility. In this work, we propose a new Attenuation Estimation Region Of Interest (AEROI) selection method for computing the ACE based on the (i) envelope signal-to-noise ratio deviation and (ii) coefficient of variation of the transmit pulse bandwidth. The method was first validated on a tissue-mimicking phantom, for which an 18%–21% reduction in the standard deviation of ACE and a 14%–24% reduction in the ACE error, expressed as a percentage of reported ACE, were obtained. A study on 59 post-delivery clinically normal placentas was then performed. The proposed AEROI selection method reduced the intra-subject standard deviation of ACE from 0.72 to 0.39 dB/cm/MHz. The measured ACE of 59 placentas was 0.77 ± 0.37 dB/cm/MHz, which establishes a baseline for future studies on placental tissue characterization.     

The infrapatellar fat pad in knee osteoarthritis: An important source of interleukin‐6 and its soluble receptor

Objective

Obesity is a potent risk factor in knee osteoarthritis (OA). It has been suggested that adipokines, secreted by adipose tissue (AT) and largely found in the synovial fluid of OA patients, derive in part from the infrapatellar fat pad (IFP), also known as Hoffa's fat pad. The goal of this study was to characterize IFP tissue in obese OA patients and to compare its features with thigh subcutaneous AT to determine whether the IFP contributes to local inflammation in knee OA via production of specific cytokines.

Methods

IFP and subcutaneous AT samples were obtained from 11 obese women (body mass index ≥30 kg/m²) with knee femorotibial OA. Gene expression was measured by real‐time quantitative polymerase chain reaction. Cytokine concentrations in plasma and in conditioned media of cultured AT explants were determined by enzyme‐linked immunosorbent assay or by Luminex xMAP technology.

Results

In IFP tissue versus subcutaneous AT, there was a decrease in the expression of genes for key enzymes implicated in adipocyte lipid metabolism, whereas the expression levels of genes for AT markers remained similar. A 2‐fold increase in the expression of the gene for interleukin‐6 (IL‐6), a 2‐fold increase in the release of IL‐6, and a 3.6‐fold increase in the release of soluble IL‐6 receptor (sIL‐6R) were observed in IFP samples, compared with subcutaneous AT, but the rates of secretion of other cytokines in IFP samples were similar to the rates in subcutaneous AT. In addition, leptin secretion was decreased by 40%, whereas adiponectin secretion was increased by 70%, in IFP samples versus subcutaneous AT.

Conclusion

Our results indicate that the IFP cytokine profile typically found in OA patients could play a role in paracrine inflammation via the local production of IL‐6/sIL‐6R and that such a profile might contribute to damage in adjacent cartilage.

     

Fetuin-A and thyroxin binding globulin predict rituximab response in rheumatoid arthritis patients with insufficient response to anti-TNFα

Clinical Rheumatology - Rheumatoid arthritis (RA) is a debilitating disease, but patient management and treatment have been revolutionized since the advent of bDMARDs. However, about one third of...